Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach.
Improved Genetic Profiling of Anthropometric Traits Using a Big Data Approach.
复制标题
DOI：
10.1371/journal.pone.0166755
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tenesa A
中科院分区：
文献类型：
--
作者：
Canela-Xandri O;Rawlik K;Woolliams JA;Tenesa A
全基因组关联研究（GWAS）承诺通过预测疾病风险为个体定制疾病管理，将其发现转化为临床有益的患者管理改进。然而，到目前为止，将GWAS的遗传发现转化为具有临床实用性并可告知临床实践的预测工具的能力令人鼓舞但有限。在这里，我们建议使用一种更强大的统计方法，由于计算要求和缺乏足够大的个体水平基因分型队列，该方法的使用传统上受到限制，但使用同一组SNP改善了对多种医学相关表型的预测。作为原理的证明，我们使用MAF > 0.05的319，038个常见SNP的共享面板来训练114，264个无关的英国白人个体的身高和四个肥胖相关特征（体重指数，基础代谢率，体脂百分比和腰臀比）的预测模型。我们得到的预测精度范围在46%和75%之间的最大可实现给定的捕获的遗传成分。对于身高，这代表了预测准确性的提高高达68%（解释了184%的表型方差），超过了先前类似规模的GWAS荟萃分析中报告的与身高稳健相关的SNP。在白色非英国人的跨人群预测是类似的白人英国人，而在亚洲和黑人个人的信息，但不太准确。我们估计，对大约50万个无关个体的基因分型将产生我们阵列中常见变异捕获的SNP遗传力的66%至82%之间的预测。预测精度没有提高时，包括罕见的SNP或多个性状联合拟合多变量模型。
Genome-wide association studies (GWAS) promised to translate their findings into clinically beneficial improvements of patient management by tailoring disease management to the individual through the prediction of disease risk. However, the ability to translate genetic findings from GWAS into predictive tools that are of clinical utility and which may inform clinical practice has, so far, been encouraging but limited. Here we propose to use a more powerful statistical approach, the use of which has traditionally been limited due to computational requirements and lack of sufficiently large individual level genotyped cohorts, but which improve the prediction of multiple medically relevant phenotypes using the same panel of SNPs. As a proof of principle, we used a shared panel of 319,038 common SNPs with MAF > 0.05 to train the prediction models in 114,264 unrelated White-British individuals for height and four obesity related traits (body mass index, basal metabolic rate, body fat percentage, and waist-to-hip ratio). We obtained prediction accuracies that ranged between 46% and 75% of the maximum achievable given the captured heritable component. For height, this represents an improvement in prediction accuracy of up to 68% (184% more phenotypic variance explained) over SNPs reported to be robustly associated with height in a previous GWAS meta-analysis of similar size. Across-population predictions in White non-British individuals were similar to those in White-British whilst those in Asian and Black individuals were informative but less accurate. We estimate that the genotyping of circa 500,000 unrelated individuals will yield predictions between 66% and 82% of the SNP-heritability captured by common variants in our array. Prediction accuracies did not improve when including rarer SNPs or when fitting multiple traits jointly in multivariate models.
登录
查看更多内容
影响因子：
30.8
作者：
Biesecker, BB;Marteau, TM
通讯作者：
Marteau, TM
影响因子：
30.8
作者：
Loh, Po-Ru;Tucker, George;Bulik-Sullivan, Brendan K.;Vilhjalmsson, Bjarni J.;Finucane, Hilary K.;Salem, Rany M.;Chasman, Daniel I.;Ridker, Paul M.;Neale, Benjamin M.;Berger, Bonnie;Patterson, Nick;Price, Alkes L.
通讯作者：
Price, Alkes L.
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Locke, Adam E.;Kahali, Bratati;Berndt, Sonja I.;Justice, Anne E.;Pers, Tune H.;Day, Felix R.;Powell, Corey;Vedantam, Sailaja;Buchkovich, Martin L.;Yang, Jian;Croteau-Chonka, Damien C.;Esko, Tonu;Fall, Tove;Ferreira, Teresa;Gustafsson, Stefan;Kutalik, Zoltan;Luan, Jian'an;Maegi, Reedik;Randall, Joshua C.;Winkler, Thomas W.;Wood, Andrew R.;Workalemahu, Tsegaselassie;Faul, Jessica D.;Smith, Jennifer A.;Zhao, Jing Hua;Zhao, Wei;Chen, Jin;Fehrmann, Rudolf;Hedman, Asa K.;Karjalainen, Juha;Schmidt, Ellen M.;Absher, Devin;Amin, Najaf;Anderson, Denise;Beekman, Marian;Bolton, Jennifer L.;Bragg-Gresham, L.;Buyske, Steven;Demirkan, Ayse;Deng, Guohong;Ehret, Georg B.;Feenstra, Bjarke;Feitosa, Mary F.;Fischer, Krista;Goel, Anuj;Gong, Jian;Jackson, Anne U.;Kanoni, Stavroula;Kleber, Marcus E.;Kristiansson, Kati;Lim, Unhee;Lotay, Vaneet;Mangino, Massimo;Leach, Irene Mateo;Medina-Gomez, Carolina;Medland, Sarah E.;Nalls, Michael A.;Palmer, Cameron D.;Pasko, Dorota;Pechlivanis, Sonali;Peters, Marjolein J.;Prokopenko, Inga;Shungin, Dmitry;Stancakova, Alena;Strawbridge, Rona J.;Sung, Yun Ju;Tanaka, Toshiko;Teumer, Alexander;Trompet, Stella;van der Laan, Sander W.;van Settee, Jessica;Van Vliet-Ostaptchouk, Jana V.;Wang, Zhaoming;Yengo, Loic;Zhang, Weihua;Isaacs, Aaron;Albrecht, Eva;Arnlov, Johan;Arscott, Gillian M.;Attwood, Antony P.;Bandinelli, Stefania;Barrett, Amy;Bas, Isabelita N.;Bellis, Claire;Bennett, Amanda J.;Berne, Christian;Blagieva, Roza;Blueher, Matthias;Bohringer, Stefan;Bonnycastle, Lori L.;Boettcher, Yvonne;Boyd, Heather A.;Bruinenberg, Marcel;Caspersen, Ida H.;Chen, Yii-Der Ida;Clarke, Robert;Daw, E. Warwick;de Craen, Anton J. M.;Delgado, Graciela;Dimitriou, Maria;Doney, Alex S. F.;Eklund, Niina;Estrada, Karol;Eury, Elodie;Folkersen, Lasse;Fraser, Ross M.;Garcia, Melissa E.;Geller, Frank;Giedraitis, Vilmantas;Gigante, Bruna;Go, Alan S.;Golay, Alain;Goodall, Alison H.;Gordon, Scott D.;Gorski, Mathias;Grabe, Hans-Joergen;Grallert, Harald;Grammer, Tanja B.;Graessler, Jurgen;Gronberg, Henrik;Groves, Christopher J.;Gusto, Gaeelle;Haessler, Jeffrey;Hall, Per;Haller, Toomas;Hallmans, Goran;Hartman, Catharina A.;Hassinen, Maija;Hayward, Caroline;Heard-Costa, Nancy L.;Helmer, Qinta;Hengstenberg, Christian;Holmen, Oddgeir;Hottenga, Jouke-Jan;James, Alan L.;Jeff, Janina M.;Johansson, Asa;Jolley, Jennifer;Juliusdottir, Thorhildur;Kinnunen, Leena;Koenig, Wolfgang;Koskenvuo, Markku;Kratzer, Wolfgang;Laitinen, Jaana;Lamina, Claudia;Leander, Karin;Lee, Nanette R.;Lichtner, Peter;Lind, Lars;Lindstrom, Jaana;Lo, Ken Sin;Lobbens, Stephane;Lorbeer, Roberto;Lu, Yingchang;Mach, Francois;Magnusson, Patrik K. E.;Mahajan, Anubha;McArdle, Wendy L.;McLachlan, Stela;Menni, Cristina;Merger, Sigrun;Mihailov, Evelin;Milani, Lili;Moayyeri, Alireza;Monda, Keri L.;Morken, Mario A.;Mulas, Antonella;Mueller, Gabriele;Mueller-Nurasyid, Martina;Musk, Arthur W.;Nagaraja, Ramaiah;Noethen, Markus M.;Nolte, Ilja M.;Pilz, Stefan;Rayner, Nigel W.;Renstrom, Frida;Rettig, Rainer;Ried, Janina S.;Ripke, Stephan;Robertson, Neil R.;Rose, Lynda M.;Sanna, Serena;Scharnagl, Hubert;Scholtens, Salome;Schumacher, Fredrick R.;Scott, William R.;Seufferlein, Thomas;Shi, Jianxin;Smith, Albert Vernon;Smolonska, Joanna;Stanton, Alice V.;Steinthorsdottir, Valgerdur;Stirrups, Kathleen;Stringham, Heather M.;Sundstrom, Johan;Swertz, Morris A.;Swift, Amy J.;Syvanen, Ann-Christine;Tan, Sian-Tsung;Tayo, Bamidele O.;Thorand, Barbara;Thorleifsson, Gudmar;Tyrer, Jonathan P.;Uh, Hae-Won;Vandenput, Liesbeth;Verhulst, Frank C.;Vermeulen, Sita H.;Verweij, Niek;Vonk, Judith M.;Waite, Lindsay L.;Warren, Helen R.;Waterworth, Dawn;Weedon, Michael N.;Wilkens, Lynne R.;Willenborg, Christina;Wilsgaard, Tom;Wojczynski, Mary K.;Wong, Andrew;Wrightl, Alan F.;Zhang, Qunyuan;Brennan, Eoin P.;Choi, Murim;Dastani, Zari;Drong, Alexander W.;Eriksson, Per;Franco-Cereceda, Anders;Gadin, Jesper R.;Gharavi, Ali G.;Goddard, Michael E.;Handsaker, Robert E.;Huang, Jinyan;Karpe, Fredrik;Kathiresan, Sekar;Keildson, Sarah;Kiryluk, Krzysztof;Kubo, Michiaki;Lee, Jong-Young;Liang, Liming;Lifton, Richard P.;Ma, Baoshan;McCarroll, Steven A.;McKnight, Amy J.;Min, Josine L.;Moffatt, Miriam F.;Montgomery, Grant W.;Murabito, Joanne M.;Nicholson, George;Nyholt, Dale R.;Okada, Yukinori;Perry, John R. B.;Dorajoo, Rajkumar;Reinmaa, Eva;Salem, Rany M.;Sandholm, Niina;Scott, Robert A.;Stolk, Lisette;Takahashi, Atsushi;Tanaka, Toshihiro;van 't Hooft, Ferdinand M.;Vinkhuyzen, Anna A. E.;Westra, Harm-Jan;Zheng, Wei;Zondervan, Krina T.;Heath, Andrew C.;Arveiler, Dominique;Bakker, Stephan J. L.;Beilby, John;Bergman, Richard N.;Blangero, John;Bovet, Pascal;Campbell, Harry;Caulfield, Mark J.;Cesana, Giancarlo;Chakravarti, Aravinda;Chasman, Daniel I.;Chines, Peter S.;Collins, Francis S.;Crawford, Dana C.;Cupples, L. Adrienne;Cusi, Daniele;Danesh, John;de Faire, Ulf;den Ruijter, Hester M.;Dominiczak, Anna F.;Erbel, Raimund;Erdmann, Jeanette;Eriksson, Johan G.;Farrall, Martin;Felix, Stephan B.;Ferrannini, Ele;Ferrieres, Jean;Ford, Ian;Forouhi, Nita G.;Forrester, Terrence;Franco, Oscar H.;Gansevoort, Ron T.;Gejman, Pablo V.;Gieger, Christian;Gottesman, Omri;Gudnason, Vilmundur;Gyllensten, Ulf;Hall, Alistair S.;Harris, Tamara B.;Hattersley, Andrew T.;Hicks, Andrew A.;Hindorff, Lucia A.;Hingorani, Aroon D.;Hofman, Albert;Homuth, Georg;Hovingh, G. Kees;Humphries, Steve E.;Hunt, Steven C.;Hypponen, Elina;Illig, Thomas;Jacobs, Kevin B.;Jarvelin, Marjo-Riitta;Joeckel, Karl-Heinz;Johansen, Berit;Jousilahti, Pekka;Jukema, J. Wouter;Jula, Antti M.;Kaprio, Jaakko;Kastelein, John J. P.;Keinanen-Kiukaanniemi, Sirkka M.;Kiemeney, Lambertus A.;Knekt, Paul;Kooner, Jaspal S.;Kooperberg, Charles;Kovacs, Peter;Kraja, Aldi T.;Kumari, Meena;Kuusisto, Johanna;Lakka, Timo A.;Langenberg, Claudia;Le Marchand, Laic;Lehtimaki, Terho;Lyssenko, Valeriya;Mannisto, Satu;Marette, Andre;Matise, Tara C.;McKenzie, Colin A.;McKnight, Barbara;Moll, Frans L.;Morris, Andrew D.;Morris, Andrew P.;Murray, Jeffrey C.;Nelis, Mari;Ohlsson, Claes;Oldehinkel, Albertine J.;Ong, Ken K.;Madden, Pamela A. F.;Pasterkamp, Gerard;Peden, John F.;Peters, Annette;Postma, Dirkje S.;Pramstaller, Peter P.;Price, Jackie F.;Qi, Lu;Raitakari, Olli T.;Rankinen, Tuomo;Rao, D. C.;Rice, Treva K.;Ridker, Paul M.;Rioux, John D.;Ritchie, Marylyn D.;Rudan, Igor;Salomaa, Veikko;Samani, Nilesh J.;Saramines, Jouko;Sarzynski, Mark A.;Schunkert, Heribert;Schwarz, Peter E. H.;Sever, Peter;Shuldiner, Alan R.;Sinisalo, Juha;Stolk, Ronald P.;Strauch, Konstantin;Toenjes, Anke;Tregouet, David-Alexandre;Tremblay, Angelo;Tremoli, Elena;Virtamo, Jarmo;Vohl, Marie-Claude;Voelker, Uwe;Waeber, Gerard;Willemsen, Gonneke;Witteman, Jacqueline C.;Zillikens, M. Carola;Adair, Linda S.;Amouyel, Philippe;Asselbergs, Folkert W.;Assimes, Themistocles L.;Bochud, Murielle;Boehm, Bernhard O.;Boerwinkle, Eric;Bornstein, Stefan R.;Bottinger, Erwin P.;Bouchard, Claude;Cauchi, Stephane;Chambers, John C.;Chanock, Stephen J.;Cooper, Richard S.;de Bakker, Paul I. W.;Dedoussis, George;Ferrucci, Luigi;Franks, Paul W.;Froguel, Philippe;Groop, Leif C.;Haiman, Christopher A.;Hamsten, Anders;Hui, Jennie;Hunter, David J.;Hveem, Kristian;Kaplan, Robert C.;Kivimaki, Mika;Kuh, Diana;Laakso, Markku;Liu, Yongmei;Martin, Nicholas G.;Maerz, Winfried;Melbve, Mads;Metspalu, Andres;Moebus, Susanne;Munroe, Patricia B.;Njolstad, Inger;Oostra, Ben A.;Palmer, Colin N. A.;Pedersen, Nancy L.;Perola, Markus;Perusse, Louis;Peters, Ulrike;Power, Chris;Quertermous, Thomas;Rauramaa, Rainer;Rivadeneira, Fernando;Saaristo, Timo E.;Saleheen, Danish;Sattar, Naveed;Schadt, Eric E.;Schlessinger, David;Slagboom, P. Eline;Snieder, Harold;Spector, Tim D.;Thorsteinsdottir, Unnu R.;Stumvoll, Michael;Tuomilehto, Jaakko;Uitterlinden, Andre G.;Uusitupa, Matti;van der Harst, Pim;Walker, Mark;Wallaschofski, Henri;Wareham, Nicholas J.;Watkins, Hugh;Weir, David R.;Wichmann, H-Erich;Wilson, James F.;Zanen, Pieter;Borecki, Ingrid B.;Deloukas, Panos;Fox, Caroline S.;Heid, Iris M.;O'Connell, Jeffrey R.;Strachan, David P.;Stefansson, Kari;van Duijri, Cornelia M.;Abecasis, Goncalo R.;Franke, Lude;Frayling, Timothy M.;McCarthy, Mark I.;Visscher, Peter M.;Scherag, Andre;Willer, Cristen J.;Boehnke, Michael;Mohlke, Karen L.;Lindgren, Cecilia M.;Beckmann, Jacques S.;Barroso, Ines;North, Kari E.;Ingelsson, Erik;Hirschhorn, Joel N.;Loos, Ruth J. F.;Speliotes, Elizabeth K.
通讯作者：
Speliotes, Elizabeth K.
影响因子：
5.8
作者：
Molinaro, AM;Simon, R;Pfeiffer, RM
通讯作者：
Pfeiffer, RM